The NMDA/D1 receptor complex as a new target in drug development

Cristina Missale, Chiara Fiorentini, Chiara Busi, Ginetta Collo, P. F. Spano

Research output: Contribution to journalArticle

Abstract

Dopamine and glutamate have been shown to extensively interact in the striatum, nucleus accumbens, hippocampus and prefrontal cortex, to regulate different physiological functions, including locomotor activity, positive reinforcement, attention and working memory. Although dysfunctions of dopamine transmission have long been identified as critical determinants of neurological and neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, there is now increasing evidence that concurrent alterations of dopamine and glutamate function may play a central role in the pathophysiology of these diseases. Thus, defining the characteristics of dopamine-glutamate interactions may be crucial to identify alternative molecular targets for the development of novel pharmacological tools. At the postsynaptic level, interactions between the dopamine D1 and the glutamate NMDA receptors appear to be particularly relevant. Different mechanisms are involved in this interactions: 1) DIR-dependent, second messenger-mediated phosphorylation of NMDAR subunits; 2) coordinated regulation of receptor trafficking at synaptic sites; 3) formation of an heteromeric D1/NMDA receptor complex. In this paper we review the molecular mechanisms, functional implications and pharmacological significance of D1R/NMDAR interaction via direct protein-protein oligomerization.

Original languageEnglish
Pages (from-to)801-808
Number of pages8
JournalCurrent Topics in Medicinal Chemistry
Volume6
Issue number8
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Bioluminescence resonance energy transfer (BRET)
  • cAMP-PKA pathway
  • Dopamine
  • Glutamate transmission
  • NMDA-mediated currents

ASJC Scopus subject areas

  • Medicine(all)
  • Chemistry(all)

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